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Trial record 37 of 58 for:    "Aspergillosis" | "Cytochrome P-450 CYP3A Inhibitors"

Individualisation of Voriconazole Antifungal Therapy Antifungal Therapy (PIVOTAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01887457
Recruitment Status : Suspended (Transfer of management of study)
First Posted : June 26, 2013
Last Update Posted : October 7, 2015
The Christie NHS Foundation Trust
Information provided by (Responsible Party):
Brynn Chappell, The Christie NHS Foundation Trust

Brief Summary:
This is a trial to determine whether giving a patient a tailored dose of voriconazole is safe and effective.

Condition or disease Intervention/treatment Phase
Immunocompromised Patient Aspergillosis Fusarium Drug: VFEND Phase 2

Detailed Description:

Invasive fungal infections are a major cause of morbidity and mortality in patients with haematological malignancy and haematopoietic stem cell transplantation.

Voriconazole is routinely used as a first-line agent for the treatment of invasive aspergillosis, invasive fusariosis and scedosporiosis. Voriconazole has extreme pharmacokinetic variability. Adult patients with a trough concentration of < 1 mg/L have a lower probability of clinical response whereas patients with trough concentrations > 6 mg/L a higher probability of toxicity.

Therapeutic drug monitoring for dose adjustment is advocated but there are no algorithms that enable voriconazole dosage to be reliably adjusted to achieve desired trough concentrations in a timely and optimally precise manner.

Novel ways to deliver optimised antifungal therapy are urgently required and this trial will evaluate whether giving a patients a tailored dose of voriconazole is safe and effective.

Plasma concentrations will be taken in real time and inputted in dose software that will calculate an optimum dose for the required trough concentration of 1-3 mg/L.

The software has been developed using data from phase I and III trials of voriconazole.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PIVOTAL: Pharmacological Individualisation of VOriconazole Therapy for AntifungaL Treatment
Study Start Date : September 2014
Estimated Primary Completion Date : November 2016
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Voriconazole
Standard adult Voriconazole (VFEND) Loading (1 hr infusion): 6mg/kg at 1 hour and 12 hours on day 1. Followed by standard maintenance dose 4mg/kg at 1 hour and 12 hours on day 2 (1 hour infusion). Day 3 follows the same schedule, expect the dose is adjusted, this dose is used on Day 4 and a further dose adjustment is made that is administered as above on Day 5.
voriconazole will be administered in iv form
Other Name: voriconazole

Primary Outcome Measures :
  1. Dose adjustment success [ Time Frame: Day 5 of treatment ]
    Dose adjustment success will be evaluated by plasma trough concentration on day 5, successful dose adjustment is defined as a trough concentration of 1-3 mg/L of voriconazole.

Secondary Outcome Measures :
  1. Mortality of patients [ Time Frame: 35 Day after starting treatment ]
    To examine the mortality of patients receiving individualised voriconazole dosing

  2. Toxicity [ Time Frame: Day 5 of treatment and 35 day follow-up ]
    To evaluate the adverse events that are attributable to voriconazole as assessed by CTCAE v4.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Any adult ≥18 years old
  • Patients where a new course of voriconazole is indicated for suspected or confirmed invasive aspergillosis or other serious fungal infections that is deemed by the treating physician to be susceptible to voriconazole
  • Patients must have venous access to permit the administration of voriconazole and enable the procurement of multiple plasma samples to measure voriconazole concentrations.
  • Estimated creatinine clearance ≥ 50 mL/min
  • Able to give written informed consent
  • Considered fit to receive the trial treatment
  • Able to remain in the hospital for at least 5 days or until they complete their trial treatment
  • Female patients must satisfy the investigator that they are not pregnant, or are not of childbearing potential, or are using adequate contraception
  • Men must also use adequate contraception

Exclusion Criteria:

  • Patients with an estimated creatinine clearance < 50 mL/minute (this precludes the use of intravenous voriconazole)
  • Patients receiving any form of renal replacement therapy i.e. haemodialysis or haemofiltration
  • Patients with hepatic insufficiency
  • Female patients that are pregnant, breast feeding or planning pregnancy during the study
  • Past history of intolerance to voriconazole
  • Age <18
  • Evidence of a clinically relevant fungal isolate that is resistant to voriconazole
  • QT prolongation on ECG
  • Use of other medications that contraindicate the use of voriconazole
  • Patients receiving any other medications that are contraindicated with the use of voriconazole i.e. terfenadine, long acting barbiturates, ergot alkaloids, etc. (Refer to SMPC). Only patients on rifampicin, rifabutin, phenytoin, and carbamazepine would have voriconazole precluded. Voriconazole influences with the pharmacokinetics of many additional agents- (see SMPC)- most importantly anti-rejection compounds- cyclosporine, tacrolimus]
  • Uncontrolled cardiac, respiratory or other disease or any serious medical or psychiatric disorder that would preclude trial therapy or informed consent.
  • Hypersensitivity to Voriconazole, its excipients or other triazoles

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01887457

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United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Brynn Chappell
The Christie NHS Foundation Trust
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Study Chair: William Hope University of Liverpool

Additional Information:
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Responsible Party: Brynn Chappell, Clinical Trials Project Manager, The Christie NHS Foundation Trust Identifier: NCT01887457     History of Changes
Other Study ID Numbers: 13_DOG06_172
2013-002578-34 ( EudraCT Number )
First Posted: June 26, 2013    Key Record Dates
Last Update Posted: October 7, 2015
Last Verified: October 2015
Keywords provided by Brynn Chappell, The Christie NHS Foundation Trust:
Additional relevant MeSH terms:
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Cytochrome P-450 CYP3A Inhibitors
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors